功能化烯胺的合成(Ⅰ):混合溶剂中硫脲催化α,β-邻位氨基溴转变成α,β-脱氢氨

Synthesis of Functionalized Enamines (Ⅰ):the α,β-Vicinal Bromoamine Compounds Converted into α,β-Dehydroamino Derivatives Catalyzed by Thiourea in Mixture Solvent

建立了一种简单有效的合成功能化烯胺的新方法.在有机小分子硫脲的催化下(50 mol%),在混合溶剂中[CH2Cl2/DMF=1∶1(V/V)],室温下各种α,β-邻位氨基溴的酮和α,β-邻位氨基溴的酯均能几乎定量的转变成相应的α,β-脱氢氨类化合物(收率90%～99%).硫脲催化邻位氨基溴转变成α,β-脱氢氨类化合物的新方法,具有反应条件温和、操作简便、收率高、催化剂廉价易得等特点.全文共考察了32种不同结构α,β-邻位氨基溴的酮和α,β-邻位氨基溴的酯反应情况,证明该方法具有广泛的适应性.实验中发现,α,β-邻位氨基溴的酮和α,β-邻位氨基溴的酯在发生消除反应时,要经过一个形成氮丙啶的中间过程,再由氮丙啶的开环反应形成最终产物(α,β-脱氢氨类化合物).因此不论反应底物为α-氨基-β-溴结构还是α-溴-β-氨基结构,通过分子内的亲核取代反应所形成的氮丙啶结构单元具有相似的立体结构,而氮丙啶的开环具有区域专一性,因此所得到的最终产物也具有区域专一性(烯键上的氨基均处在羰基的α-位).所提出的硫脲催化邻位氨基溴转变成α,β-脱氢氨的可能机理,很好地解释了该反应的区域专一性.所有的产物结构均经过了1H NMR,13C NMR及高分辨质谱的确证.

An easy and efficient new method for the synthesis of functionalized enamines from α,β-vicinal bromoamine ketones and esters has been developed.A series of α,β-vicinal bromoamine ketones and esters can be smoothly converted into corresponding α,β-dehydroamino derivatives catalyzed by thiourea（50 mol%） in mixture solvents [CH2Cl2/DMF=1∶1（V/V）] at room temperature in nearly quantitative yield（90%～99%）.This new method,the conversion of α,β-vicinal bromoamine ketones and esters into α,β-dehydroamino derivatives,has many advantages such as mild conditions,easy handling,nearly quantitative yields etc.32 structurally different substrates were investigated.The results indicated that the protocol has applicability in a large scope of vicinal bromoamine compounds including α,β-vicinal bromoamine ketones and esters.During the elimination process of HBr from vicinal bromoamine compounds to generate corresponding functionalized enamines with assistance of thiourea,the corresponding intermediate aziridines must be formed firstly.The final products（α,β-dehydroamino derivatives） were formed via ring-open reaction of the aziridines.Herein,no matter the substrate was α-amino-β-bromo or α-bromo-β-amino in structurally,the aziridines skeleton in structurally was similar to each other formed from the intramolecular nucleophilic replacement reaction fashion.Because of ring-open reactions of aziridines have full regiospecificity,the obtained final products are full regiospecificity,too.A possible mechanism was proposed and it can explain well the full regiospecificity of the reaction.All functionalized enamines were obtained by following experimental procedure.Unless otherwise stated,all reagents were purchased from commercial sources and used without further purification.A mixture of a α,β-vicinal bromoamine ketones or esters（1.0 mmol）,anhydrous K2CO3（0.5 mmol）,thiourea（0.5 mmol） was put into a dried convenience vessel.Then,10 mL of commercial and not degassed mixture solvent [CH2Cl2/DMF=1∶1（V/V）] was added to the vessel with stirring at room temperature without protection of inert gas.The reaction progress was monitored by TLC until the starting material was consumed,and the spot of final product was not changed（The first spot represented a corresponding aziridine.Subsequently,this aziridine spot was disappeared,and the final product spot was formed which was stable）.After completion of the reaction,the reaction mixture was diluted with EtOAc（15 mL） and washed with water（15 mL×3） and brine（15 mL×3）.The organic layer was dried by anhydrous Na2SO4 and concentrated under reduced pressure to give crude product,which was purified by column chromatography packed with silica gel with petroleum ether and EtOAc as eluent to afford pure product.The structures of all products were confirmed by their 1H NMR,13 C NMR and HRMS analysis.